Carbohydrate-Based Azacrown Ethers in Asymmetric Syntheses

Carbohydrate-based crown ethers represent a special group of chiral phase transfer catalysts. Several derivatives of these macrocycles have been synthesized in our research group. Among these compounds, monoaza-15-crown-5 lariat ethers proved to be effective phase transfer and enantioselective catalysts in certain reactions. Those chiral azacrown ethers incorporating various carbohydrate moieties in the macrocyclic structure are reviewed, which generated asymmetric induction in reactions, such as Michael addition, epoxidation of enones, Darzens condensation and Michael-initiated ring-closure (MIRC) reaction. Effects on the catalytic activity of the structural changes are the focus.

Enantioselective Michael Addition of Malonates to Enones

: Many catalysts were tested in asymmetric Michael additions in order to synthesize enantioenriched products. One of the most common reaction types among the Michael reactions is the conjugated addition of malonates to enones making it possible to investigate the structure–activity relationship of the catalysts. The most commonly used Michael acceptors are chalcone, substituted chalcones, chalcone derivatives, cyclic enones, while typical donors may be dimethyl, diethyl, dipropyl, diisopropyl, dibutyl, di-tert-butyl and dibenzyl malonates. This review summarizes the most important enantioselective catalysts applied in these types of reactions.

The Synthesis of Hydrobenzoin-Based Monoaza Crown Ethers and Their Application as Recyclable Enantioselective Catalysts

New recyclable monoaza-15-crown ethers have been synthesized starting from (R,R)-(+)- and (S,S)-(−)-hydrobenzoin. These macrocycles proved to be efficient and reusable phase transfer catalysts in a few asymmetric reactions under mild conditions. The asymmetric epoxidation of trans-chalcone took place with up to 81% ee, while using other chalcone derivatives, the products were formed with 68–88% ee. The hydrobenzoin-based lariat ethers were also tested in the cyclopropanation of a few electron deficient olefins using diethyl bromomalonate to afford the product with good enantioselectivities (54–75% ee). The catalysts were recovered by salt formation, followed by extraction, and were reused without the loss of the activity and effect on the enantioselectivity. Graphic Abstract The synthesis of hydrobenzoin-based monaza crown ethers and their application as recyclable enantioselective catalysts.

Single- and multi-component chiral supraparticles as modular enantioselective catalysts

Nanoscale biological assemblies exemplified by exosomes, endosomes and capsids, play crucial roles in all living systems. Supraparticles (SP) from inorganic nanoparticles (NPs) replicate structural characteristics of these bioassemblies, but it is unknown whether they can mimic their biochemical functions. Here, we show that chiral ZnS NPs self-assemble into 70–100 nm SPs that display sub-nanoscale porosity associated with interstitial spaces between constituent NPs. Similarly to photosynthetic bacterial organelles, these SPs can serve as photocatalysts, enantioselectively converting L- or D-tyrosine (Tyr) into dityrosine (diTyr). Experimental data and molecular dynamic simulations indicate that the chiral bias of the photocatalytic reaction is associated with the chiral environment of interstitial spaces and preferential partitioning of enantiomers into SPs, which can be further enhanced by co-assembling ZnS with Au NPs. Besides replicating a specific function of biological nanoassemblies, these findings establish a path to enantioselective oxidative coupling of phenols for biomedical and other needs.

Scalable Synthesis of a Chiral Selenium π-Acid Catalyst and Its Use in Enantioselective Iminolactonization of β,γ-Unsaturated Amides

Chiral selenium π-acid catalysis has for a long time been lagging behind other areas of asymmetric catalysis due to a lack of highly enantioselective catalysts. In this regard, we recently developed the first chiral selenium π-acid catalyst which performs the oxidative cyclization of β,γ-unsaturated carboxylic acids with high enantioselectivities. We report herein our improved synthesis of this chiral selenium catalyst, which allows access to a large quantity of the catalyst as the diselenide. In addition, the catalyst is tested in the oxidative cyclization of N-methoxy β,γ-unsaturated amides to give iminolactones with high enantioselectivities.